The etiology of childhood leukemia, the most common pediatric cancer, remains unknown. Benzene is a known leukemogen in adults and ambient air exposures to this carcinogen have been hypothesized to play a role in the incidence of childhood leukemia and other air toxics may be implicated as well. This investigation will represent the largest study conducted to date to assess effects of air toxic exposures on the risk of early childhood acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Moreover, the methodological component of the application will critically assess differences in exposure assignment due to changes in residence from the time of birth to the time of diagnosis. Texas provides a unique study area to assess cancer risk associated with exposures to air toxics because of its extensive road traffic and the number of petrochemical facilities and coal-fired power plants that operate in the state. The state also ranks poorly in the nation in terms of health, social and economic disparities. A case- control study design with control for individual- and neighborhood-level confounders will be employed. Cases between the ages of 0-4 years will be identified from the Texas Cancer Registry and controls sampled from Texas birth certificate records. Residential exposure to air toxics will be assessed using modeled estimates of census-tract ambient air levels of benzene, 1,3-butadiene and polycyclic aromatic hydrocarbons (PAHs) from the U.S. EPA's National-Scale Air Toxics Assessment. The first aim will be to assess the association between risk of ALL and AML and ambient air pollution using modeled census-tract level estimates of benzene, 1,3- butadiene and PAHs. Combined effects of these air pollutants will also be evaluated. Because studies of ambient air pollution and pediatric outcomes often rely on maternal address at delivery that is available from the birth certificate to classify exposure, the second aim will evaluate differences in exposure assignment based on maternal address at the time of birth and address of the child at the time of diagnosis. The proposed study is significant in that it will (1) enhance our understanding of putative risks o childhood leukemia associated with air toxics and (2) aid epidemiologists in considerations of the impact of residential mobility from birth to diagnosis in future studies of childhood leukemia and other pediatric outcomes. Results will inform risk assessors and policy makers about combined effects arising from multiple chemical stressors, aid in the development of interventions to reduce risks of childhood leukemia associated with air pollution, and provide a framework for evaluating the potential for exposure misclassification due to residential mobility. PUBLIC HEALTH RELEVANCE: This investigation will represent the largest study conducted to date to assess effects of air toxic exposures on the risk of early childhood acute myeloid leukemia and acute lymphocytic leukemia. Our study will enhance our understanding of putative risks of childhood leukemia associated with air toxics and will also assess differences in exposure assignment based on maternal address at delivery and address of the child at the time of diagnosis. Results will inform risk assessors and policy makers about combined effects arising from multiple chemical stressors, aid in the development of interventions to reduce risks of childhood leukemia associated with air pollution, and provide a framework for evaluating the potential for exposure misclassification due to residential mobility.